The research program is focused on mechanisms of excitotoxicity- induced chronic central pain (CCP) after SCI. The rodent contusion model of SCI will be used for assessing CCP and to explore the contributions of excitatory amino acid (EAA)-mediated mechanisms that lead to cell death after SCI. We hypothesize that damage caused by the elevated levels of EAA is causally related to the development of chronic pain as well as other dysfunctional states after SCI. The three projects will test molecular, biochemical and functional outcomes of interrupting EAA release of transport mechanisms and inhibiting EAA receptor- mediated processes, including apoptosis, in a combination of approaches. Project 1 will assess behavioral outcome and AA receptor and transporter distribution and density following blockage of EAA mediated processes and interventions of apoptotic pathways after SCI. Project 2 will measure EAA concentrations acutely after contusion injury and examine the role after EAA release, receptors and transporters play in neuronal loss after SCI. Project 3 will measure the expression levels of early genes (p50, p65, p49) activated by glutamate receptor-mediated mechanisms and the resulting downstream changes in expression of genes (Bcl-2 gene family) that influence neural cell survival after SCI. There are three cores: an administrative core, an animal core and a morphology core. The results for these studies will guide the development of strategic interventions to improve functional outcome after SCI.